GLORIA

GEOMAR Library Ocean Research Information Access

X
feed icon rss

Your email was sent successfully. Check your inbox.

An error occurred while sending the email. Please try again.

Proceed reservation?

Export
Filter
  • The American Physiological Society (APS)  (22)
  • American Society of Hematology (ASH)  (12)
  • BMJ Publishing Group  (8)
  • 2020-2023
  • 2010-2014  (42)
Document type
Keywords
Publisher
Years
Year
  • 1
    facet.materialart.
    Unknown
    DEPTOR ubiquitination and destruction by SCF{beta}-TrCP (2012)
    The American Physiological Society (APS)
    Details
    Publication Date: 2012-07-16
    Description: β-Transducin repeats-containing protein (β-TrCP) is the substrate recognition subunit of the SCF (SKP1, CUL1, and F-box protein)-type E3 ubiquitin ligase complex. SCF β-TrCP ubiquitinates specifically phosphorylated substrates to promote their subsequent destruction by the 26S proteasome and plays a critical role in various human diseases including tumorigenesis. We and others (Duan S et al. Mol Cell 44: 317–324, 2011; Gao D et al. Mol Cell 44: 290–303, 2011; Zhao Y et al. Mol Cell 44: 304–316, 2011) recently reported that SCF β-TrCP regulates cell growth and autophagy by controlling the ubiquitination and destruction of DEPTOR, an endogenous mammalian target of rapamycin inhibitor, in a phosphorylation-dependent manner. In this review, we discuss β-TrCP's new downstream substrate, DEPTOR, as well as summarize the novel functional aspects of β-TrCP in controlling cell growth and regulating autophagy, in part through governing the stability of DEPTOR.
    Print ISSN: 0193-1849
    Electronic ISSN: 1522-1555
    Topics: Medicine
    Published by The American Physiological Society (APS)
    Location Call Number Limitation Availability
    BibTip Others were also interested in ...
    PAPER CURRENT
  • 2
    facet.materialart.
    Unknown
    Multiple residues in the distal C terminus of the {alpha}-subunit have roles in modulating human epithelial sodium channel activity (2012)
    The American Physiological Society (APS)
    Details
    Publication Date: 2012-07-16
    Description: Epithelial sodium channels (ENaC) are critically important in the regulation of ion and fluid balance in both renal and respiratory epithelia. ENaC functional polymorphisms may contribute to alterations in blood pressure in the general population. We previously reported that the A663T polymorphism in the C terminus of the α-subunit altered ENaC functional and surface expression in Xenopus laevis oocytes (Samaha FF, Rubenstein RC, Yan W, Ramkumar M, Levy DI, Ahn YJ, Sheng S, Kleyman TR. J Biol Chem 279: 23900–23907, 2004). We examined whether sites in the vicinity of 663 influenced channel activity by performing scanning Ala mutagenesis. Interestingly, only αT663/G667Aβ channels exhibited increased currents compared with αT663β. This increase in channel activity reflected an increase in channel open probability and not an increase in channel surface expression. In contrast, decreases in channel activity were observed with both αT663/C664Aβ and αT663/C664Mβ channels. The decrease in functional expression of αT663/C664Mβ channels correlated with decreased surface expression, suggesting that the αC664M mutation altered the intracellular trafficking of the channel. While cytoplasmic Cys residues may be modified by the addition of palmitate, we did not observe palmitoylation of αC664. Our results suggest that multiple residues in the distal part of the cytoplasmic C terminus have roles in modulating channel activity.
    Print ISSN: 1931-857X
    Electronic ISSN: 1522-1466
    Topics: Medicine
    Published by The American Physiological Society (APS)
    Location Call Number Limitation Availability
    BibTip Others were also interested in ...
    PAPER CURRENT
  • 3
    facet.materialart.
    Unknown
    HIF-1{alpha} deletion partially rescues defects of hematopoietic stem cell quiescence caused by Cited2 deficiency (2012)
    American Society of Hematology (ASH)
    In: Blood
    Details
    Publication Date: 2012-03-23
    Description: Cited2 is a transcriptional modulator involved in various biologic processes including fetal liver hematopoiesis. In the present study, the function of Cited2 in adult hematopoiesis was investigated in conditional knockout mice. Deletion of Cited2 using Mx1-Cre resulted in increased hematopoietic stem cell (HSC) apoptosis, loss of quiescence, and increased cycling, leading to a severely impaired reconstitution capacity as assessed by 5-fluorouracil treatment and long-term transplantation. Transcriptional profiling revealed that multiple HSC quiescence- and hypoxia-related genes such as Egr1 , p57 , and Hes1 were affected in Cited2-deficient HSCs. Because Cited2 is a negative regulator of HIF-1, which is essential for maintaining HSC quiescence, and because we demonstrated previously that decreased HIF-1 α gene dosage partially rescues both cardiac and lens defects caused by Cited2 deficiency, we generated Cited2 and HIF-1 α double-knockout mice. Additional deletion of HIF-1 α in Cited2 -knockout BM partially rescued impaired HSC quiescence and reconstitution capacity. At the transcriptional level, deletion of HIF-1 α restored expression of p57 and Hes1 but not Egr1 to normal levels. Our results suggest that Cited2 regulates HSC quiescence through both HIF-1–dependent and HIF-1–independent pathways.
    Keywords: Hematopoiesis and Stem Cells
    Print ISSN: 0006-4971
    Electronic ISSN: 1528-0020
    Topics: Biology , Medicine
    Published by American Society of Hematology (ASH)
    Location Call Number Limitation Availability
    BibTip Others were also interested in ...
    PAPER CURRENT
  • 4
    facet.materialart.
    Unknown
    Connective tissue growth factor regulates adipocyte differentiation of mesenchymal stromal cells and facilitates leukemia bone marrow engraftment (2013)
    American Society of Hematology (ASH)
    In: Blood
    Details
    Publication Date: 2013-07-19
    Description: Mesenchymal stromal cells (MSCs) are a major component of the leukemia bone marrow (BM) microenvironment. Connective tissue growth factor (CTGF) is highly expressed in MSCs, but its role in the BM stroma is unknown. Therefore, we knocked down (KD) CTGF expression in human BM-derived MSCs by CTGF short hairpin RNA. CTGF KD MSCs exhibited fivefold lower proliferation compared with control MSCs and had markedly fewer S-phase cells. CTGF KD MSCs differentiated into adipocytes at a sixfold higher rate than controls in vitro and in vivo. To study the effect of CTGF on engraftment of leukemia cells into BM, an in vivo model of humanized extramedullary BM (EXM-BM) was developed in NOD/SCID/IL-2rg null mice. Transplanted Nalm-6 or Molm-13 human leukemia cells engrafted at a threefold higher rate in adipocyte-rich CTGF KD MSC-derived EXM-BM than in control EXM-BM. Leptin was found to be highly expressed in CTGF KD EXM-BM and in BM samples of patients with acute myeloid and acute lymphoblastic leukemia, whereas it was not expressed in normal controls. Given the established role of the leptin receptor in leukemia cells, the data suggest an important role of CTGF in MSC differentiation into adipocytes and of leptin in homing and progression of leukemia.
    Keywords: Hematopoiesis and Stem Cells, Myeloid Neoplasia, Lymphoid Neoplasia
    Print ISSN: 0006-4971
    Electronic ISSN: 1528-0020
    Topics: Biology , Medicine
    Published by American Society of Hematology (ASH)
    Location Call Number Limitation Availability
    BibTip Others were also interested in ...
    PAPER CURRENT
  • 5
    facet.materialart.
    Unknown
    Activation of cannabinoid receptor 2 inhibits experimental cystitis (2013)
    The American Physiological Society (APS)
    Details
    Publication Date: 2013-05-16
    Description: Cannabinoids have been shown to exert analgesic and anti-inflammatory effects, and the effects of cannabinoids are mediated primarily by cannabinoid receptors 1 and 2 (CB1and CB2). Both CB1 and CB2 are present in bladders of various species, including human, monkey, and rodents, and it appears that CB2 is highly expressed in urothelial cells. We investigated whether treatment with the CB2 agonist GP1a alters severity of experimental cystitis induced by acrolein and referred mechanical hyperalgesia associated with cystitis. We also investigated whether the mitogen-activated protein kinases (MAPK), ERK1/2, p38, and JNK are involved in the functions of CB2. We found that treatment with the selective CB2 agonist GP1a (1–10 mg/kg, ip) inhibited the severity of bladder inflammation 3 h after intravesical instillation of acrolein in a dose-dependent manner, and inhibition reached significance at a dose of 10 mg/kg ( P 〈 0.05). Treatment with GP1a (10 mg/kg) inhibited referred mechanical hyperalgesia associated with cystitis ( P 〈 0.05). The inhibitory effects of the CB2 agonist were prevented by the selective CB2 antagonist AM630 (10 mg/kg, sc). We further demonstrated the inhibitory effects of CB2 appear to be at least partly mediated by reducing bladder inflammation-induced activation of ERK1/2 MAPK pathway. The results of the current study indicate that CB2 is a potential therapeutic target for treatment of bladder inflammation and pain in patients.
    Print ISSN: 0363-6119
    Electronic ISSN: 1522-1490
    Topics: Medicine
    Published by The American Physiological Society (APS)
    Location Call Number Limitation Availability
    BibTip Others were also interested in ...
    PAPER CURRENT
  • 6
    facet.materialart.
    Unknown
    Does Helicobacter pylori eradication really reduce the risk of gastric cancer at the population level? (2013)
    BMJ Publishing Group
    In: Gut
    Details
    Publication Date: 2013-05-01
    Description: The development of gastric cancer is related to multiple factors, including gene, diet, environment and Helicobacter pylori infection. The Maastricht IV consensus stated that the eradication of H pylori reduces the risk of gastric cancer development. 1 Although the results from epidemiological and animal studies support this statement, no existing human clinical trial has resulted in the same outcome. However, H pylori eradication for gastric cancer prevention is still recommended in the consensus (recommendation level 1C). We believe it may be premature to put forward such a statement based on existing evidence. To investigate whether enough evidence exists to support H pylori eradication at the population level, we examined the randomised controlled clinical trials (RCTs) referenced in the consensus. The RCT conducted by Wong et al 2 was one of the studies used to support the recommendation. This cohort had the longest follow-up period (7.5 years), but the...
    Print ISSN: 0017-5749
    Electronic ISSN: 1468-3288
    Topics: Medicine
    Published by BMJ Publishing Group
    Location Call Number Limitation Availability
    BibTip Others were also interested in ...
    PAPER CURRENT
  • 7
    facet.materialart.
    Unknown
    Prognostic impact and targeting of CRM1 in acute myeloid leukemia (2013)
    American Society of Hematology (ASH)
    In: Blood
    Details
    Publication Date: 2013-05-17
    Description: Chromosomal region maintenance 1 (CRM1) is a nuclear export receptor recognizing proteins bearing a leucine-rich nuclear export signal. CRM1 is involved in nuclear export of tumor suppressors such as p53. We investigated the prognostic significance of CRM1 in acute myeloid leukemia (AML) and effects of a novel small-molecule selective inhibitor of CRM1. CRM1 protein expression was determined in 511 newly diagnosed AML patients and was correlated with mouse double minute 2 (MDM2) and p53 levels. High CRM1 expression was associated with short survival of patients and remained an adverse prognostic factor in multivariate analysis. CRM1 inhibitor KPT-185 induced mainly full-length p53 and apoptosis in a p53-dependent manner, whereas inhibition of proliferation was p53 independent. Patient samples with p53 mutations showed low sensitivity to KPT-185. Nuclear retention of p53 induced by CRM1 inhibition synergized with increased levels of p53 induced by MDM2 inhibition in apoptosis induction. KPT-185 and Nutlin-3a, alone and in combination, induced synergistic apoptosis in patient-derived CD34 + /CD38 – AML, but not in normal progenitor cells. Data suggest that CRM1 exerts an antiapoptotic function and is highly prognostic in AML. We propose a novel combinatorial approach for the therapy of AML, aimed at maximal activation of p53-mediated apoptosis by concomitant MDM2 and CRM1 inhibition.
    Keywords: Myeloid Neoplasia
    Print ISSN: 0006-4971
    Electronic ISSN: 1528-0020
    Topics: Biology , Medicine
    Published by American Society of Hematology (ASH)
    Location Call Number Limitation Availability
    BibTip Others were also interested in ...
    PAPER CURRENT
  • 8
    facet.materialart.
    Unknown
    Direct and indirect protection of right ventricular function by estrogen in an experimental model of pulmonary arterial hypertension (2014)
    The American Physiological Society (APS)
    Details
    Publication Date: 2014-08-02
    Description: Pulmonary arterial hypertension (PAH) results in right ventricular (RV) dysfunction and failure. Paradoxically, women are more frequently diagnosed with PAH but have better RV systolic function and survival rates than men. The mechanisms by which sex differences alter PAH outcomes remain unknown. Here, we sought to study the role of estrogen in RV functional remodeling in response to PAH. The SU5416-hypoxia (SuHx) mouse model of PAH was used. To study the role of estrogen, female mice were ovariectomized and then treated with estrogen or placebo. SuHx significantly increased RV afterload and resulted in RV hypertrophy. Estrogen treatment attenuated the increase in RV afterload compared with the untreated group (effective arterial elastance: 2.3 ± 0.1 mmHg/μl vs. 3.2 ± 0.3 mmHg/μl), and this was linked to preserved pulmonary arterial compliance (compliance: 0.013 ± 0.001 mm 2 /mmHg vs. 0.010 ± 0.001 mm 2 /mmHg; P 〈 0.05) and decreased distal muscularization. Despite lower RV afterload in the estrogen-treated SuHx group, RV contractility increased to a similar level as the placebo-treated SuHx group, suggesting an inotropic effect of estrogen on RV myocardium. Consequently, when compared with the placebo-treated SuHx group, estrogen improved RV ejection fraction and cardiac output (ejection fraction: 57 ± 2% vs. 44 ± 2% and cardiac output: 9.7 ± 0.4 ml/min vs. 7.6 ± 0.6 ml/min; P 〈 0.05). Our study demonstrates for the first time that estrogen protects RV function in the SuHx model of PAH in mice directly by stimulating RV contractility and indirectly by protecting against pulmonary vascular remodeling. These results underscore the therapeutic potential of estrogen in PAH.
    Print ISSN: 0363-6135
    Electronic ISSN: 1522-1539
    Topics: Medicine
    Published by The American Physiological Society (APS)
    Location Call Number Limitation Availability
    BibTip Others were also interested in ...
    PAPER CURRENT
  • 9
    facet.materialart.
    Unknown
    Lamivudine/telbivudine-associated neuromyopathy: neurogenic damage, mitochondrial dysfunction and mitochondrial DNA depletion (2014)
    BMJ Publishing Group
    Details
    Publication Date: 2014-10-17
    Description: Aims Myopathy or neuropathy has been associated with lamivudine/telbivudine therapy in hepatitis B patients. We aim to describe the pathological changes of lamivudine/telbivudine-associated neuromyopathy. Methods We retrospectively recruited six patients who were diagnosed with nucleotide analogues-associated myopathy or neuropathy. Muscle and nerve biopsy were performed, and the specimens were prepared for the light microscopy and electron microscopy. Genomic DNA was extracted from frozen muscle specimens, and the mitochondrial DNA (mtDNA) content was quantified by real-time PCR. Results Recovery of the myopathy can be achieved after the discontinuation or changing the drugs to entecavir. Muscle and nerve biopsy revealed similar changes under either the light or electronic microscopy in all the subjects. Quantitative real-time PCR revealed decrease of mtDNA content in the affected muscle. Conclusions MtDNA depletion results in mitochondrial dysfunction in the lamivudine/telbivudine-associated neuromyopathy. Myopathy was characterised by mitochondrial dysfunction accompanied with neurogenic damage due to axonal neuropathy. Ultrastructure changes of mitochondria included vacuolisation, simplification of the cristae and homogenised matrix.
    Keywords: Liver disease, Open access, Hepatitis and other GI infections, Muscle disease, Musculoskeletal syndromes, Hepatitis (sexual health), Clinical diagnostic tests
    Print ISSN: 0021-9746
    Electronic ISSN: 1472-4146
    Topics: Medicine
    Published by BMJ Publishing Group
    Location Call Number Limitation Availability
    BibTip Others were also interested in ...
    PAPER CURRENT
  • 10
    facet.materialart.
    Unknown
    Exome sequencing identifies SLC17A9 pathogenic gene in two Chinese pedigrees with disseminated superficial actinic porokeratosis (2014)
    BMJ Publishing Group
    Details
    Publication Date: 2014-09-13
    Description: Background Disseminated superficial actinic porokeratosis (DSAP) is a rare autosomal dominant genodermatosis characterised by annular lesions that has an atrophic centre and a prominent peripheral ridge distributed on sun exposed area. It exhibits high heterogeneity, and five linkage loci have been reported. The mevalonate kinase ( MVK ) gene located on 12q24 has been confirmed as one of the disease-causing genes. But, the pathogenesis of a large part of DSAP remains unclear so far. Methods The recruited with DSAP carried no MVK coding mutations. Exome sequencing was performed in two affected and one unaffected individual in Family 1. Cosegregation of the candidate variants was tested in other family members. Sanger sequencing in 33 individuals with familial DSAP and 19 sporadic DSAP individuals was performed for validating the causative gene. Results An average of 1.35 x 10 5 variants were generated from exome data and 133 novel NS/SS/indels were identified as being shared by two affected individuals but absent in the unaffected individual. After functional prediction, 25 possible deleterious variants were identified. In Family 1, a missense variant c.932G〉A (p.Arg311Gln) in exon 10 of SLC17A9 was observed in cosegregation with the phenotype; this amino acid substitution was located in a highly conserved major facilitator superfamily (MFS) domain in multiple mammalian. One additional missense variant c.25C〉T (p.Arg9Cys) in exon 2 of SLC17A9 was found in Family 2. Conclusions The result identified SLC17A9 as another pathogenic gene for DSAP, which suggests a correlation between the aberrant vesicular nucleotide transporter and the pathogenesis of DSAP.
    Keywords: Molecular genetics, Dermatology
    Print ISSN: 0022-2593
    Electronic ISSN: 1468-6244
    Topics: Medicine
    Published by BMJ Publishing Group
    Location Call Number Limitation Availability
    BibTip Others were also interested in ...
    PAPER CURRENT
Close ⊗
This website uses cookies and the analysis tool Matomo. More information can be found here...